Molecular analysis presents many challenges depending upon the specific application and nature of the material being analyzed. In many cases, a portable analysis instrument is very useful as well as one of low cost, however, traditional instruments for high accuracy liquid analysis, for example, tend to be larger laboratory instruments, which by their nature are also expensive. Traditional laboratory instruments also tend to require relatively large sample amounts, and for instruments using thermal analysis methods, a relatively long analysis time, which limits throughput in some applications.
With regard to different thermal analysis techniques, a MEMS-based solution could address a number of existing problems. Some popular thermoanalytical techniques include Differential Thermal Analysis (DTA) and Differential Scanning calorimetry (DSC). In DTA, the material under study and a reference material are made to undergo identical thermal cycles, while recording any temperature difference between sample and reference. This differential temperature is then plotted against time, or against temperature (a DTA curve or thermogram). Changes in the sample, for example, enthalpy changes or specific heat changes, can be detected relative to the inert reference. Thus, a DTA curve provides data on the transformations that have occurred such as glass transitions, crystallization, melting, and sublimation.
When applied to chemical sensors and analytical instruments, a sample of an analyte (or a combination of analytes) is captured on a primary sensor probe or element and then heated in a controlled manner. Variations in the measured temperature signal from the probe are caused by adsorbed heat due to a combination of melting, evaporation, and decomposition or other phase changes, which can produce a distinct temperature profile for each analyte when compared with a signal from an identical probe that has no analytes present and that is heated in an identical manner. Subtracting the reference response from the signal given off by the primary probe produces the data of interest as a result. Sometimes instead of having no material, the reference probe may analyze an amount of an inert or neutral substance, such as a buffer solution in the case of some forms of liquid analysis.
Another form of calorimetry called “differential scanning calorimetry” or “DSC” is similar to DTA. DSC is a thermoanalytical technique in which the amount of heat required to increase the temperature of a sample is measured and compared to a reference as a function of temperature. Both the sample and reference are maintained at nearly the same temperature throughout the experiment. Generally, the temperature program for a DSC analysis is designed such that the sample holder temperature increases linearly as a function of time. The reference sample should have a well-defined heat capacity over the range of temperatures to be scanned. The term DSC was coined to describe an instrument that measures energy directly and allows precise measurements of heat capacity.
The basic principle underlying this technique is that when the sample undergoes a physical transformation, such as any type of phase transition, more or less heat will need to flow to it compared to the reference to maintain both at the same temperature. Whether less or more heat must flow to the sample depends on whether the transformation process is exothermic or endothermic. For example, in many cases, as a solid sample melts to a liquid, it will require more heat flowing to the sample to increase its temperature at the same rate as the reference. This is due to the absorption of heat by the sample as it undergoes an endothermic phase transition from solid to liquid. Likewise, as the sample undergoes an exothermic processes (such as crystallization), less heat can be required to raise the sample temperature. By observing the difference in heat flow between the sample and reference, differential scanning calorimeters are able to measure the amount of heat absorbed or released during such transitions. DSC may also be used to observe more subtle phase changes, such as glass transitions. DSC is widely used in industrial settings as a quality control instrument due to its applicability in evaluating sample purity and for studying polymer curing. In the field of biology, DSC is often used to study denaturing of samples such as protein unfolding, and the unbinding of molecules such as the unbinding of antibody-antigen pairs or the uncoupling of DNA strands.
Where multiple sensor probes or transducers are included in a single miniature array such as in a MEMS array constructed using semiconductor fabrication techniques, isolation of a reference probe can sometimes require additional size, complexity, and cost in order to properly isolate the reference probe. Traditional DTA and DSC methodologies of utilizing separate primary and reference probes have the additional negative characteristic where any subtle physical differences between the primary measurement probe and the reference probe may introduce errors into the DTA or DSC measurement result. For applications where a separate reference cell is definitely required, micro-fabrication will help to reduce variation between a sample cell and a reference cell and also reduce the cost of the reference cell, due to the small size and the simultaneous fabrication of the sample cell and the reference cell.
Accordingly, there is a need for new and/or improved MEMS devices and methods for molecular analysis of chemicals and other materials that can overcome the aforementioned drawbacks.